HIV-1 gp120 accelerates Fas-mediated activation-induced human lamina propria T cell apoptosis.
Intestinal mucosa represents an important portal of entry of HIV and a site of virus reservoir and active replication. Recently, in HIV patients, an early depletion of intestinal lamina propria T lymphocytes (LPT) has been described. HIV-1 gp120 has been demonstrated to promote apoptosis in noninfected isolated peripheral blood T cells, therefore we investigated whether gpl20 modulates apoptosis of normal human intestinal lamina propria T cells. Purified T cells were obtained by immunomagnetic negative selection from human lamina propria mononuclear cells isolated from surgical specimens by enzymatic procedure. Cells were incubated with or without recombinant gpl20 (10 microg/ml) and cultured either in the absence of any stimulus or in the presence of plate-bound anti-CD3 Ab (OKT3) or soluble anti-CD2 Ab (T11(2) + T11[3]). Apoptosis was assessed by flow cytometric analysis after propidium iodide staining. We demonstrated that preincubation of normal LPT cells with HIV-1 gpl20 accelerates the apoptosis observed during CD2-pathway stimulation of LPT cells. This process is mediated by Fas/Fas ligand interaction and related to an increased induction of Fas ligand mRNA by gpl20. Therefore HIV-1 gp120 could contribute to the depletion of noninfected LPT cells inducing a premature cell death.
Boirivant
M
M
Immunology Department, Istituto Superiore di Sanità, Rome, Italy.
Viora
M
M
Giordani
L
L
Luzzati
A L
AL
Pronio
A M
AM
Montesani
C
C
Pugliese
O
O
D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D018801:CD2 Antigens / Q000502:physiology; D015704:CD4 Antigens / Q000494:pharmacology; D003106:Colon / Q000276:immunology; D053222:Fas Ligand Protein; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000494:pharmacology; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D007422:Intestines / Q000166:cytology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000494:pharmacology; D009092:Mucous Membrane / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
D018801:CD2 Antigens; D015704:CD4 Antigens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D015699:HIV Envelope Protein gp120; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor